Allergic and other immune mechanisms have been suggested as important in the etiology and pathogenesis of otitis media with effusion (OME) and both humoral and cellular components of the immune response have been identified in middle ear effusion (MEE) obtained from patients with OME. Yet, specific and direct documentation of an immune basis for OME has not been forthcoming. In order to establish a causal relationship between an immune hypersensitivity and middle ear pathophysiology, a provocative intranasal antigen challenge test has been designed using 9-step inflation-deflation tympanometric test for eustachian tube dysfunction (ETD). Preliminary double blind crossover studies have documented the development of reversible ETD after intranasal pollen challenge in 8 adults with pollen allergic rhinitis: 50% of these patients upon natural exposure to pollen developed ETD as measured by 9-step tympanometry during pollen season. Our aims are to confirm and extend these studies to document antigen induced ETD in allergic adults and children and establish a clinical relevance for antigen induced ETD. Since questions concerning the etiology and pathogenesis required invasive techniques and are not suitable in man, a monkey animal model has also been developed. Studies by our group have shown that in the monkey a surgically created ETD will induce OME and that an IgE mediated allergic response can induce OME or ETD in the monkey depending on the antigen challenge. Our specific aims will be to further develop the monkey model of OME employing IgE and other immune reactions in monkeys with normal ET function or compromised, surgically created ET function. The experimental MEE will be assayed for immune components, including IgA and its secretory piece, IgG, IgM and IgE, total complement, C3 and C4, and cells including polys, eosinophils and lymphocytes (both T and B cells). Since OME is mainly a disease of the young child, it is essential that age related differences be explored in each aspect of our experimental model. The reversal and prevention of ETD and/or OME with several drugs, including cromolyn, steroids and antihistamines will be studied in man and the monkey model.